TAGRISSO® (osimertinib) plenary presentation
will demonstrate significantly improved overall survival for
patients with early-stage resectable EGFR-mutated lung
cancer
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
will show potential across a broad range of advanced
HER2-expressing advanced cancers
LYNPARZA® (olaparib) and IMFINZI®
(durvalumab) combination will demonstrate delay in progression in
newly diagnosed advanced ovarian cancer without a tumor BRCA
mutation
AstraZeneca advances its ambition to revolutionize cancer care
with new data across its industry-leading portfolio of cancer
medicines at the American Society of Clinical Oncology (ASCO)
Annual Meeting, June 2 to 6, 2023.
More than 130 abstracts will feature 22 approved and potential
new medicines across the Company’s diverse oncology portfolio and
pipeline, including 11 oral presentations and a late-breaking
plenary presentation of overall survival (OS) results from the
ADAURA Phase III trial of TAGRISSO® (osimertinib) in the adjuvant
treatment of patients with early-stage epidermal growth factor
receptor-mutated (EGFRm) lung cancer.
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: “Our unwavering commitment to continually
raising the standard of cancer care for patients with high unmet
needs is evident in our data at ASCO this year. With our leading
portfolio of medicines in lung cancer, our ambition is to have the
right AstraZeneca medicine for more than half of all patients with
this disease by 2030. We will showcase significant steps toward
that goal with overall survival data from ADAURA that reinforce
TAGRISSO as the backbone therapy in EGFR-mutated lung cancer.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “We are extending the benefits of our
practice-changing cancer medicines, including TAGRISSO, IMFINZI and
LYNPARZA, while also investing in new scientific platforms such as
T-cell engagers and cell therapy to attack cancer from multiple
angles and advance the next wave of options for patients. At ASCO,
the extraordinary momentum for our antibody drug conjugate
collaboration portfolio continues with data for ENHERTU
underscoring its potential across many HER2-expressing tumor types
beyond breast, lung and gastric, and updated results for
datopotamab deruxtecan that reinforce our confidence in this
TROP2-directed treatment.”
Improving outcomes across lung cancer settings
A late-breaking plenary presentation will showcase OS results
from the ADAURA Phase III trial evaluating TAGRISSO in early-stage
(IB, II and IIIA) EGFR-mutated non-small cell lung cancer
(NSCLC).
Several posters will describe trials-in-progress of IMFINZI®
(durvalumab) that further reinforce the Company’s progress toward
moving lung cancer treatment to earlier stages of disease. These
include NeoCOAST-2 evaluating IMFINZI in multiple novel
immunotherapy combinations in resectable, early-stage NSCLC;
PACIFIC-4 in combination with standard of care stereotactic body
radiation therapy in medically unresectable Stage I/II NSCLC;
PACIFIC-8 in combination with anti-TIGIT monoclonal antibody
domvanalimab in unresectable Stage III NSCLC; and PACIFIC-9 in
combination with novel immunotherapies oleclumab or monalizumab in
patients with unresectable Stage III NSCLC.
Additionally, several presentations and posters will highlight
the Company’s commitment to improving outcomes in advanced lung
cancer with next-wave treatments and novel combinations. These
include:
- An oral presentation of updated results from the TROPION-Lung02
Phase Ib dose escalation and expansion trial of datopotamab
deruxtecan (Dato-DXd) in combination with pembrolizumab with or
without platinum chemotherapy in patients with previously untreated
or pretreated, advanced or metastatic NSCLC without actionable
genomic alterations. TROPION-Lung02 is the first trial to show
results for an antibody drug conjugate (ADC) plus an immune
checkpoint inhibitor combination with or without chemotherapy in
this setting.
- Interim results from the ARTEMIDE-01 Phase I trial assessing
rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in
patients with advanced or metastatic NSCLC. The Company is
advancing rilvegostomig into Phase III development this year.
- A trial-in-progress poster describing the EGRET Phase I trial,
a first-in-human study evaluating AZD9592, an EGFR/cMET bispecific
ADC, in patients with advanced solid tumors including in
combination with TAGRISSO in metastatic EGFRm NSCLC. This is the
Company’s first bispecific ADC to enter the clinic and has shown a
promising efficacy and safety profile in preclinical models.
- A trial-in-progress poster describing the LATIFY Phase III
trial of ceralasertib, an ataxia telangiectasia and rad3-related
(ATR) kinase inhibitor, plus IMFINZI in patients with locally
advanced or metastatic NSCLC who progressed on or after
anti-PD-(L)1 and platinum-based therapy. This combination has
previously demonstrated promising efficacy in this setting in the
ongoing HUDSON Phase II trial.
- A trial-in-progress poster detailing the TROPION-Lung04 Phase
Ib dose escalation and expansion study of datopotamab deruxtecan in
various immunotherapy combinations with or without carboplatin in
patients with previously untreated advanced or metastatic NSCLC,
including recently initiated cohorts with bispecific
immunotherapies rilvegostomig and volrustomig.
Showcasing the potential of ENHERTU® (fam-trastuzumab
deruxtecan-nxki) across multiple HER2-expressing tumors
Several presentations will reinforce the potential of ENHERTU in
a broad range of HER2-expressing tumors with significant unmet
need, including gynecological, genitourinary, gastrointestinal and
breast cancers.
A late-breaking oral presentation of interim results from the
DESTINY-PanTumor02 Phase II trial will highlight the efficacy and
safety of ENHERTU in heavily pretreated patients across multiple
HER2-expressing advanced solid tumors including biliary tract,
bladder, cervical, endometrial, ovarian, pancreatic, and rare
cancers. In March, ENHERTU met the prespecified target for
objective response rate and demonstrated durable responses across
multiple HER2-expressing tumor types in this trial.
Additionally, an oral presentation of primary results from the
DESTINY-CRC02 Phase II trial will be presented, demonstrating the
safety and efficacy of ENHERTU in patients with HER2-positive
advanced colorectal cancer with progression following
standard-of-care treatment. This trial was initiated based on
positive data for ENHERTU in the DESTINY-CRC01 Phase II trial.
Another oral presentation will feature a pooled benefit-risk
analysis from the DESTINY-Breast01, 02 and 03 trials of ENHERTU in
patients with breast cancer aged 65 and older compared to those
younger than 65.
Potential to transform outcomes across tumors by attacking
cancer from multiple angles
A late-breaking oral presentation will feature interim
progression-free survival (PFS) results from the DUO-O Phase III
trial evaluating a combination of LYNPARZA® (olaparib), IMFINZI,
chemotherapy and bevacizumab in newly diagnosed patients with
advanced high-grade epithelial ovarian cancer without tumor BRCA
mutations. In April, it was announced that DUO-O demonstrated a
statistically significant and clinically meaningful improvement in
PFS for this LYNPARZA and IMFINZI combination versus chemotherapy
plus bevacizumab alone.
Data will be also shared from a post-hoc exploratory analysis of
the SERENA-2 Phase II trial in patients with advanced ER-positive
breast cancer who have disease recurrence or progression after
endocrine therapy. The analysis will show PFS data for patients
treated with next-generation selective estrogen receptor degrader
(ngSERD) camizestrant versus fulvestrant based on the type of ESR1
mutation at baseline, detected via circulating tumor DNA.
Previously presented primary results from SERENA-2 demonstrated PFS
benefit with camizestrant irrespective of ESR1 mutation status or
prior treatment with CDK4/6 inhibitors.
Data will also be shared from a matching-adjusted indirect
comparison (MAIC) of the efficacy and safety of CALQUENCE®
(acalabrutinib) versus zanubrutinib in relapsed or refractory
chronic lymphocytic leukemia, based on data from the ASCEND and
ALPINE Phase III trials.
In addition, interim Phase I results evaluating AZD0486
(TNB-486), a CD19/CD3 next-generation T-cell engager, will show the
potential of targeting CD19 in heavily pretreated patients with
follicular lymphoma.
Results from a Phase Ib/II dose escalation and expansion trial
of the novel immunotherapy oleclumab in combination with IMFINZI
and chemotherapy will also be presented in patients with metastatic
pancreatic cancer, including those with high levels of CD73
expression.
A poster discussion will feature health-related quality-of-life
results from the PROpel Phase III trial of LYNPARZA plus
abiraterone in patients with metastatic castration-resistant
prostate cancer.
Two presentations will focus on immune-mediated adverse events
(imAEs) in the HIMALAYA Phase III trial of IMFINZI plus IMJUDO®
(tremelimumab-actl) in 1st-line unresectable liver cancer,
including an oral presentation on outcomes by imAE occurrence and a
poster on temporal patterns of imAE occurrence.
Collaboration in the scientific community is critical to
improving outcomes for patients. AstraZeneca is collaborating with
Daiichi Sankyo Company Limited to develop and commercialize ENHERTU
and datopotamab deruxtecan; with Merck & Co., Inc., known as
MSD outside of the US and Canada, to develop and commercialize
LYNPARZA. AstraZeneca obtained full oncology rights to monalizumab
from Innate Pharma in October 2018 through a co-development and
commercialization agreement initiated in 2015.
Key AstraZeneca presentations during ASCO 2023
Lead
Author
Abstract
Title
Presentation
details (CDT)
Tumor drivers and resistance
Herbst, R
Overall survival analysis from the ADAURA
trial of adjuvant osimertinib in patients with resected EGFR
mutated‑ (EGFRm) stage IB–IIIA non-small cell lung cancer
(NSCLC).
Abstract #LBA3
Plenary Session
June 4, 2023
2:17pm
Oliveira, M
Clinical activity of camizestrant, a
next-generation SERD, versus fulvestrant in patients with a
detectable ESR1 mutation: Exploratory analysis of the SERENA-2
Phase 2 trial.
Abstract #1066
Poster Session
Breast Cancer—Metastatic
June 4, 2023
8:00am
Antibody drug conjugates
Meric-Bernstam, F
Efficacy and safety of trastuzumab
deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid
tumors: DESTINY-PanTumor02 (DP-02) interim results.
Abstract #LBA3000
Oral Abstract Session Developmental
Therapeutics—Molecularly Targeted Agents and Tumor Biology
June 5, 2023
8:00am
Raghav, K
Trastuzumab deruxtecan (T-DXd) in patients
(pts) with HER2-overexpressing/amplified (HER2+) metastatic
colorectal cancer (mCRC): Primary results from the multicenter,
randomized, Phase 2 DESTINY-CRC02 study.
Abstract #3501
Oral Abstract Session Gastrointestinal
Cancer—Colorectal and Anal
June 4, 2023
8:12am
Krop, I
An age-specific pooled analysis of
trastuzumab deruxtecan (T‑DXd) in patients (pts) with HER2-positive
(HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02,
and -03.
Abstract #1006
Oral Abstract Session Breast
Cancer—Metastatic
June 5, 2023
1:30pm
Goto, Y
TROPION-Lung02: Datopotamab deruxtecan
(Dato-DXd) plus pembrolizumab (pembro) with or without platinum
chemotherapy (Pt-CT) in advanced non-small cell lung cancer
(aNSCLC).
Abstract #9004
Oral Abstract Session Lung
Cancer—Non-Small Cell Metastatic
June 6, 2023
10:57am
Aggarwal, C
EGRET: A first-in-human study of the novel
antibody-drug conjugate (ADC) AZD9592 as monotherapy or combined
with other anticancer agents in patients (pts) with advanced solid
tumors.
Abstract #TPS3156
Poster Session Developmental
Therapeutics—Molecularly Targeted Agents and Tumor Biology
June 3, 2023
8:00am
Borghaei, H
TROPION-Lung04: Phase 1b, multicenter
study of datopotamab deruxtecan (Dato-DXd) in combination with
immunotherapy ± carboplatin in advanced/metastatic non-small cell
lung cancer (mNSCLC).
Abstract#TPS3158
Poster Session Developmental
Therapeutics—Molecularly Targeted Agents and Tumor Biology
June 3, 2023
8:00am
DNA damage response
Harter, P
Durvalumab with paclitaxel/carboplatin
(PC) and bevacizumab (bev), followed by maintenance durvalumab,
bev, and olaparib in patients (pts) with newly diagnosed advanced
ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm):
Results from the randomized, placebo (pbo)-controlled Phase III
DUO-O trial.
Abstract #LBA5506
Oral Abstract Session Gynecologic
Cancer
June 3, 2023
5:12pm
Armstrong, A
Health-related quality of life (HRQoL) and
pain outcomes for patients (pts) with metastatic
castration-resistant prostate cancer (mCRPC) who received
abiraterone (abi) and olaparib (ola) versus (vs) abi and placebo
(pbo) in the Phase III PROpel trial.
Abstract #5012
Poster Discussion Genitourinary
Cancer—Prostate, Testicular, and Penile Session
June 3, 2023
1:27pm
Immuno-Oncology
Hübner, H
RNA expression levels from peripheral
immune cells, a minimally invasive liquid biopsy source to predict
response to therapy, survival and immune-related adverse events in
patients with triple negative breast cancer enrolled in the
GeparNuevo trial.
Abstract #1011
Oral Abstract Session
Clinical Science Symposium: Harnessing the
Breast Cancer Immune Response
June 3, 2023
1:51pm
Lau, G
Outcomes by occurrence of immune-mediated
adverse events (imAEs) with tremelimumab (T) plus durvalumab (D) in
the Phase 3 HIMALAYA study in unresectable hepatocellular carcinoma
(uHCC).
Abstract #4004
Oral Abstract Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 2, 2023
3:57pm
Besse, B
LATIFY: Phase 3 study of ceralasertib +
durvalumab vs docetaxel in patients with locally advanced or
metastatic non-small-cell lung cancer that progressed on or after
anti-PD-(L)1 and platinum-based therapy.
Abstract #TPS9161
Poster Session Lung Cancer—Non-Small Cell
Metastatic
June 4, 2023
8:00am (CDT)
Rohrberg, K
Safety, pharmacokinetics (PK),
pharmacodynamics (PD) and preliminary efficacy of AZD2936, a
bispecific antibody targeting PD-1 and TIGIT, in checkpoint
inhibitor (CPI)-experienced advanced/metastatic non-small-cell lung
cancer (NSCLC): First report of ARTEMIDE-01.
Abstract #9050
Poster Session Lung Cancer—Non-Small Cell
Metastatic
June 4, 2023
8:00am
Guisier, F
NeoCOAST-2: A Phase 2 study of neoadjuvant
durvalumab plus novel immunotherapies (IO) and chemotherapy (CT) or
MEDI5752 (volrustomig) plus CT, followed by surgery and adjuvant
durvalumab plus novel IO or volrustomig alone in patients with
resectable non-small-cell lung cancer (NSCLC).
Abstract #TPS8604
Poster Session Lung Cancer—Non-Small Cell
Local Regional/Small Cell/Other Thoracic Cancers
June 4, 2023
8:00am
Robinson, C
Phase 3 study of durvalumab with SBRT for
unresected stage I/II, lymph-node negative NSCLC
(PACIFIC-4/RTOG3515).
Abstract #TPS8607
Poster Session Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic Cancers
June 4, 2023
8:00am
Özgüroğlu, M
Phase 3 trial of durvalumab combined with
domvanalimab following concurrent chemoradiotherapy (cCRT) in
patients with unresectable stage III NSCLC (PACIFIC-8).
Abstract #TPS8609
Poster Session Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic Cancers
June 4, 2023
8:00am
Barlesi, F
Phase 3 study of durvalumab combined with
oleclumab or monalizumab in patients with unresectable stage III
NSCLC (PACIFIC-9).
Abstract #TPS8610
Poster Session Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic Cancers
June 4, 2023
8:00am
Ganti, A
The prognostic value of patient reported
outcomes (PROs) and clinical/demographic variables in the CASPIAN
study.
Abstract #8516
Poster Discussion Session Lung
Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic
Cancers
June 4, 2023
11:45am
Lau, G
Temporal patterns of immune-mediated
adverse events (imAEs) with tremelimumab (T) plus durvalumab (D) in
the Phase 3 HIMALAYA study in unresectable hepatocellular carcinoma
(uHCC).
Abstract #4073
Poster Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 5, 2023
8:00am
Coveler, A
Safety and clinical activity of oleclumab
(O) ± durvalumab (D) + chemotherapy (CT) in patients (pts) with
metastatic pancreatic ductal adenocarcinoma (mPDAC): A Phase 1b/2
randomized study.
Abstract #4136
Poster Session Gastrointestinal
Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
June 5, 2023
8:00am
Hematology
Kittai, A
A matching-adjusted indirect comparison
(MAIC) of the efficacy and safety of acalabrutinib (acala) versus
zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic
leukemia (RR CLL).
Abstract #7540
Poster Session Hematologic
Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
June 5, 2023
8:00am
Nair, R
High complete response rate with TNB-486
in relapsed/refractory follicular lymphoma: Interim results an
ongoing Phase 1 study.
Abstract #7524
Poster Session Hematologic
Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
June 5, 2023
8:00am
SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)
- There are no contraindications for TAGRISSO
- TAGRISSO is associated with several serious and sometimes fatal
adverse reactions, including interstitial lung disease
(ILD)/pneumonitis, QTc interval prolongation, cardiomyopathy,
keratitis, erythema multiforme and Stevens-Johnson syndrome,
cutaneous vasculitis, aplastic anemia, and embryo-fetal
toxicity
- The most common (≥20%) adverse reactions, including lab
abnormalities, were leukopenia, lymphopenia, thrombocytopenia,
diarrhea, anemia, rash, musculoskeletal pain, nail toxicity,
neutropenia, dry skin, stomatitis, fatigue, and cough
INDICATIONS
- TAGRISSO is indicated as adjuvant therapy after tumor resection
in adult patients with non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test
- TAGRISSO is indicated for the first-line treatment of adult
patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have epidermal growth factor receptor (EGFR) exon 19
deletions or exon 21 L858R mutations, as detected by an
FDA-approved test
- TAGRISSO is indicated for the treatment of adult patients with
metastatic EGFR T790M mutation-positive NSCLC, as detected by an
FDA-approved test, whose disease has progressed on or after EGFR
tyrosine kinase inhibitor (TKI) therapy
Please see the complete Important Safety Information on
tagrisso.com and complete Prescribing
Information, including Patient Information for
TAGRISSO.
IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab
deruxtecan-nxki)
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor
conjugate indicated for the treatment of adult patients with:
- Unresectable or metastatic HER2-positive breast cancer who have
received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and
have developed disease recurrence during or within six months of
completing therapy
- Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-)
breast cancer, as determined by an FDA-approved test, who have
received a prior chemotherapy in the metastatic setting or
developed disease recurrence during or within 6 months of
completing adjuvant chemotherapy
- Unresectable or metastatic non-small cell lung cancer (NSCLC)
whose tumors have activating HER2 (ERBB2) mutations, as detected by
an FDA-approved test, and who have received a prior systemic
therapy
This indication is approved under accelerated approval based on
objective response rate and duration of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
- Locally advanced or metastatic HER2-positive gastric or
gastroesophageal junction adenocarcinoma who have received a prior
trastuzumab-based regimen
WARNING: INTERSTITIAL LUNG DISEASE and
EMBRYO-FETAL TOXICITY
- Interstitial lung disease (ILD) and pneumonitis, including
fatal cases, have been reported with ENHERTU. Monitor for and
promptly investigate signs and symptoms including cough, dyspnea,
fever, and other new or worsening respiratory symptoms. Permanently
discontinue ENHERTU in all patients with Grade 2 or higher
ILD/pneumonitis. Advise patients of the risk and to immediately
report symptoms.
- Exposure to ENHERTU during pregnancy can cause embryo-fetal
harm. Advise patients of these risks and the need for effective
contraception.
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease
(ILD), including pneumonitis, can occur in patients treated with
ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has
been observed in patients with moderate renal impairment. Advise
patients to immediately report cough, dyspnea, fever, and/or any
new or worsening respiratory symptoms. Monitor patients for signs
and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate
patients with suspected ILD by radiographic imaging. Consider
consultation with a pulmonologist. For asymptomatic ILD/pneumonitis
(Grade 1), interrupt ENHERTU until resolved to Grade 0, then if
resolved in ≤28 days from date of onset, maintain dose. If resolved
in >28 days from date of onset, reduce dose one level. Consider
corticosteroid treatment as soon as ILD/pneumonitis is suspected
(e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic
ILD/pneumonitis (Grade 2 or greater), permanently discontinue
ENHERTU. Promptly initiate systemic corticosteroid treatment as
soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day
prednisolone or equivalent) and continue for at least 14 days
followed by gradual taper for at least 4 weeks.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC
treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients.
Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of
patients treated with ENHERTU. Median time to first onset was 5
months (range: 0.9 to 23).
Locally Advanced or Metastatic Gastric
Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD
occurred in 10% of patients. Median time to first onset was 2.8
months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in
patients treated with ENHERTU. Monitor complete blood counts prior
to initiation of ENHERTU and prior to each dose, and as clinically
indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC]
<1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade
2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5
x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then
reduce dose by one level. For febrile neutropenia (ANC <1.0 x
109/L and temperature >38.3º C or a sustained temperature of
≥38º C for more than 1 hour), interrupt ENHERTU until resolved,
then reduce dose by one level.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC
treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was
reported in 65% of patients. Sixteen percent had Grade 3 or 4
decreased neutrophil count. Median time to first onset of decreased
neutrophil count was 22 days (range: 2 to 664). Febrile neutropenia
was reported in 1.1% of patients.
Locally Advanced or Metastatic Gastric
Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a
decrease in neutrophil count was reported in 72% of patients.
Fifty-one percent had Grade 3 or 4 decreased neutrophil count.
Median time to first onset of decreased neutrophil count was 16
days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of
patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of
developing left ventricular dysfunction. Left ventricular ejection
fraction (LVEF) decrease has been observed with anti-HER2
therapies, including ENHERTU. Assess LVEF prior to initiation of
ENHERTU and at regular intervals during treatment as clinically
indicated. Manage LVEF decrease through treatment interruption.
When LVEF is >45% and absolute decrease from baseline is 10-20%,
continue treatment with ENHERTU. When LVEF is 40-45% and absolute
decrease from baseline is <10%, continue treatment with ENHERTU
and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and
absolute decrease from baseline is 10-20%, interrupt ENHERTU and
repeat LVEF assessment within 3 weeks. If LVEF has not recovered to
within 10% from baseline, permanently discontinue ENHERTU. If LVEF
recovers to within 10% from baseline, resume treatment with ENHERTU
at the same dose. When LVEF is <40% or absolute decrease from
baseline is >20%, interrupt ENHERTU and repeat LVEF assessment
within 3 weeks. If LVEF of <40% or absolute decrease from
baseline of >20% is confirmed, permanently discontinue ENHERTU.
Permanently discontinue ENHERTU in patients with symptomatic
congestive heart failure. Treatment with ENHERTU has not been
studied in patients with a history of clinically significant
cardiac disease or LVEF <50% prior to initiation of
treatment.
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg)
In patients with metastatic breast cancer and HER2-mutant NSCLC
treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.6%
of patients, of which 0.4% were Grade 3.
Locally Advanced or Metastatic Gastric
Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no
clinical adverse events of heart failure were reported; however, on
echocardiography, 8% were found to have asymptomatic Grade 2
decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant
woman. Advise patients of the potential risks to a fetus. Verify
the pregnancy status of females of reproductive potential prior to
the initiation of ENHERTU. Advise females of reproductive potential
to use effective contraception during treatment and for 7 months
after the last dose of ENHERTU. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with ENHERTU and for 4 months after the last dose
of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L)
interrupt ENHERTU until resolved to Grade 1 or less, then maintain
dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L)
interrupt ENHERTU until resolved to Grade 1 or less, then reduce
dose by one level.
Adverse Reactions
Metastatic Breast Cancer and HER2-Mutant
NSCLC (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4
mg/kg intravenously every 3 weeks in 984 patients in Study
DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast03,
DESTINY-Breast04, and DESTINY-Lung02. Among these patients 65% were
exposed for >6 months and 39% were exposed for >1 year. In
this pooled safety population, the most common (≥20%) adverse
reactions, including laboratory abnormalities, were nausea (76%),
decreased white blood cell count (71%), decreased hemoglobin (66%),
decreased neutrophil count (65%), decreased lymphocyte count (55%),
fatigue (54%), decreased platelet count (47%), increased aspartate
aminotransferase (48%), vomiting (44%), increased alanine
aminotransferase (42%), alopecia (39%), increased blood alkaline
phosphatase (39%), constipation (34%), musculoskeletal pain (32%),
decreased appetite (32%), hypokalemia (28%), diarrhea (28%), and
respiratory infection (24%).
HER2-Positive Metastatic Breast
Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with
unresectable or metastatic HER2-positive breast cancer who received
at least one dose of ENHERTU 5.4 mg/kg intravenously every three
weeks in DESTINY-Breast03. The median duration of treatment was 14
months (range: 0.7 to 30).
Serious adverse reactions occurred in 19% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were vomiting, interstitial lung disease,
pneumonia, pyrexia, and urinary tract infection. Fatalities due to
adverse reactions occurred in 0.8% of patients including COVID-19
and sudden death (one patient each).
ENHERTU was permanently discontinued in 14% of patients, of
which ILD/pneumonitis accounted for 8%. Dose interruptions due to
adverse reactions occurred in 44% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, leukopenia, anemia,
thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis.
Dose reductions occurred in 21% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
reduction were nausea, neutropenia, and fatigue.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (76%), decreased white blood cell count
(74%), decreased neutrophil count (70%), increased aspartate
aminotransferase (67%), decreased hemoglobin (64%), decreased
lymphocyte count (55%), increased alanine aminotransferase (53%),
decreased platelet count (52%), fatigue (49%), vomiting (49%),
increased blood alkaline phosphatase (49%), alopecia (37%),
hypokalemia (35%), constipation (34%), musculoskeletal pain (31%),
diarrhea (29%), decreased appetite (29%), respiratory infection
(22%), headache (22%), abdominal pain (21%), increased blood
bilirubin (20%), and stomatitis (20%).
HER2-Low Metastatic Breast
Cancer
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with
unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast
cancer who received ENHERTU 5.4 mg/kg intravenously every 3 weeks
in DESTINY-Breast04. The median duration of treatment was 8 months
(range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in 28% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea,
musculoskeletal pain, sepsis, anemia, febrile neutropenia,
hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to
adverse reactions occurred in 4% of patients including
ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic
colitis, disseminated intravascular coagulation, dyspnea, febrile
neutropenia, general physical health deterioration, pleural
effusion, and respiratory failure (1 patient each).
ENHERTU was permanently discontinued in 16% of patients, of
which ILD/pneumonitis accounted for 8%. Dose interruptions due to
adverse reactions occurred in 39% of patients treated with ENHERTU.
The most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, fatigue, anemia, leukopenia,
COVID-19, ILD/pneumonitis, increased transaminases, and
hyperbilirubinemia. Dose reductions occurred in 23% of patients
treated with ENHERTU. The most frequent adverse reactions (>2%)
associated with dose reduction were fatigue, nausea,
thrombocytopenia, and neutropenia.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (76%), decreased white blood cell count
(70%), decreased hemoglobin (64%), decreased neutrophil count
(64%), decreased lymphocyte count (55%), fatigue (54%), decreased
platelet count (44%), alopecia (40%), vomiting (40%), increased
aspartate aminotransferase (38%), increased alanine
aminotransferase (36%), constipation (34%), increased blood
alkaline phosphatase (34%), decreased appetite (32%),
musculoskeletal pain (32%), diarrhea (27%), and hypokalemia
(25%).
Unresectable or Metastatic HER2-Mutant
NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and
6.4 mg/kg [n=50]); however, only the results for the recommended
dose of 5.4 mg/kg intravenously every 3 weeks are described below
due to increased toxicity observed with the higher dose in patients
with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with
unresectable or metastatic HER2-mutant NSCLC who received ENHERTU
5.4 mg/kg intravenously every three weeks in DESTINY‑Lung02.
Nineteen percent of patients were exposed for >6 months.
Serious adverse reactions occurred in 30% of patients receiving
ENHERTU. Serious adverse reactions in >1% of patients who
received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea,
nausea, pleural effusion, and increased troponin I. Fatality
occurred in 1 patient with suspected ILD/pneumonitis (1%).
ENHERTU was permanently discontinued in 8% of patients. Adverse
reactions which resulted in permanent discontinuation of ENHERTU
were ILD/pneumonitis, diarrhea, hypokalemia, hypomagnesemia,
myocarditis, and vomiting. Dose interruptions of ENHERTU due to
adverse reactions occurred in 23% of patients. Adverse reactions
which required dose interruption (>2%) included neutropenia and
ILD/pneumonitis. Dose reductions due to an adverse reaction
occurred in 11% of patients.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were nausea (61%), decreased white blood cell count
(60%), decreased hemoglobin (58%), decreased neutrophil count
(52%), decreased lymphocyte count (43%), decreased platelet count
(40%), decreased albumin (39%), increased aspartate
aminotransferase (35%), increased alanine aminotransferase (34%),
fatigue (32%), constipation (31%), decreased appetite (30%),
vomiting (26%), increased alkaline phosphatase (22%), and alopecia
(21%).
Locally Advanced or Metastatic Gastric
Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally
advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma
in DESTINY-Gastric01. Patients intravenously received at least one
dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either
irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2
weekly for 3 weeks. The median duration of treatment was 4.6 months
(range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in 44% of patients receiving
ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients
who received ENHERTU were decreased appetite, ILD, anemia,
dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor
hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of
patients: disseminated intravascular coagulation, large intestine
perforation, and pneumonia occurred in one patient each (0.8%).
ENHERTU was permanently discontinued in 15% of patients, of
which ILD accounted for 6%. Dose interruptions due to adverse
reactions occurred in 62% of patients treated with ENHERTU. The
most frequent adverse reactions (>2%) associated with dose
interruption were neutropenia, anemia, decreased appetite,
leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia,
upper respiratory tract infection, diarrhea, and hypokalemia. Dose
reductions occurred in 32% of patients treated with ENHERTU. The
most frequent adverse reactions (>2%) associated with dose
reduction were neutropenia, decreased appetite, fatigue, nausea,
and febrile neutropenia.
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were decreased hemoglobin (75%), decreased white
blood cell count (74%), decreased neutrophil count (72%), decreased
lymphocyte count (70%), decreased platelet count (68%), nausea
(63%), decreased appetite (60%), increased aspartate
aminotransferase (58%), fatigue (55%), increased blood alkaline
phosphatase (54%), increased alanine aminotransferase (47%),
diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation
(24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia
(22%).
Use in Specific Populations
- Pregnancy: ENHERTU can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risks to a fetus. There are clinical considerations if ENHERTU is
used in pregnant women, or if a patient becomes pregnant within 7
months after the last dose of ENHERTU.
- Lactation: There are no data regarding the presence of
ENHERTU in human milk, the effects on the breastfed child, or the
effects on milk production. Because of the potential for serious
adverse reactions in a breastfed child, advise women not to
breastfeed during treatment with ENHERTU and for 7 months after the
last dose.
- Females and Males of Reproductive Potential:
Pregnancy testing: Verify pregnancy
status of females of reproductive potential prior to initiation of
ENHERTU. Contraception: Females:
ENHERTU can cause fetal harm when administered to a pregnant woman.
Advise females of reproductive potential to use effective
contraception during treatment with ENHERTU and for 7 months after
the last dose. Males: Advise male patients with female partners of
reproductive potential to use effective contraception during
treatment with ENHERTU and for 4 months after the last dose.
Infertility: ENHERTU may impair male
reproductive function and fertility.
- Pediatric Use: Safety and effectiveness of ENHERTU have
not been established in pediatric patients.
- Geriatric Use: Of the 883 patients with breast cancer
treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.6% were
≥75 years. No overall differences in efficacy within clinical
studies were observed between patients ≥65 years of age compared to
younger patients. There was a higher incidence of Grade 3-4 adverse
reactions observed in patients aged ≥65 years (60%) as compared to
younger patients (48%). Of the 101 patients with unresectable or
metastatic HER2-mutant NSCLC treated with ENHERTU 5.4 mg/kg, 40%
were ≥65 years and 8% were ≥75 years. No overall differences in
efficacy or safety were observed between patients ≥65 years of age
compared to younger patients. Of the 125 patients with locally
advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma
treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65
years and 14% were ≥75 years. No overall differences in efficacy or
safety were observed between patients ≥65 years of age compared to
younger patients.
- Renal Impairment: A higher incidence of Grade 1 and 2
ILD/pneumonitis has been observed in patients with moderate renal
impairment. Monitor patients with moderate renal impairment more
frequently. The recommended dosage of ENHERTU has not been
established for patients with severe renal impairment (CLcr <30
mL/min).
- Hepatic Impairment: In patients with moderate hepatic
impairment, due to potentially increased exposure, closely monitor
for increased toxicities related to the topoisomerase inhibitor.
The recommended dosage of ENHERTU has not been established for
patients with severe hepatic impairment (total bilirubin >3
times ULN and any AST).
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi
Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or
fda.gov/medwatch.
Please see Full Prescribing Information,
including Boxed WARNINGS, and Medication
Guide.
SELECT SAFETY INFORMATION FOR LYNPARZA® (olaparib)
LYNPARZA is indicated:
- as maintenance therapy for women with
BRCAm* advanced ovarian cancer after response to platinum-based
chemotherapy
- in combination with bevacizumab as
maintenance therapy for women with HRD+* advanced ovarian cancer
after response to platinum-based chemotherapy
- as maintenance treatment of women with
recurrent ovarian cancer after response to platinum-based
chemotherapy
- for the adjuvant treatment of adult
patients with deleterious or suspected deleterious gBRCAm,*
HER2-negative high-risk early breast cancer who have been treated
with neoadjuvant or adjuvant chemotherapy
- for the treatment of patients with gBRCAm,*
HER2-negative metastatic breast cancer after receiving chemotherapy
in the neoadjuvant, adjuvant, or metastatic setting and endocrine
therapy, if appropriate
- as maintenance therapy for gBRCAm*
metastatic pancreatic cancer that has not progressed cancer after
16 weeks of platinum-based chemotherapy
- for the treatment of patients with HRR
gene-mutated* metastatic castration-resistant prostate cancer who
have progressed following prior treatment with enzalutamide or
abiraterone
*Select patients for this indication based on an FDA-approved
companion diagnostic.
Select Safety Information
- Serious and potentially fatal adverse events included:
- Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML):
Monitor patients for hematological toxicity at baseline and monthly
thereafter. Discontinue if MDS/AML is confirmed
- Pneumonitis: Interrupt treatment if pneumonitis is suspected.
Discontinue if pneumonitis is confirmed
- Venous Thromboembolic Events: Including severe or fatal
pulmonary embolism (PE). Monitor patients for signs and symptoms of
venous thrombosis and PE, and treat as medically appropriate
- Advise patients of the potential risk of embryo-fetal toxicity
and to use effective contraception
- Most common adverse reactions (≥10%) in clinical trials:
- as a single agent were nausea, fatigue (including asthenia),
anemia, vomiting, diarrhea, decreased appetite, headache,
dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia,
leukopenia, and thrombocytopenia
- in combination with bevacizumab were nausea, fatigue (including
asthenia), anemia, lymphopenia, vomiting, diarrhea, neutropenia,
leukopenia, urinary tract infection, and headache
Please see the complete Important Safety Information on
lynparza.com and complete Prescribing
Information, including Medication Guide.
IMPORTANT SAFETY INFORMATION FOR IMFINZI® (durvalumab) and
IMJUDO® (tremelimumab-actl)
There are no contraindications for IMFINZI® (durvalumab) or
IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under
Warnings and Precautions may not include all possible severe and
fatal immune-mediated reactions. Immune-mediated adverse reactions,
which may be severe or fatal, can occur in any organ system or
tissue. Immune-mediated adverse reactions can occur at any time
after starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate clinical
chemistries including liver enzymes, creatinine,
adrenocorticotropic hormone (ACTH) level, and thyroid function at
baseline and before each dose. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO
depending on severity. See USPI Dosing and Administration for
specific details. In general, if IMFINZI and IMJUDO requires
interruption or discontinuation, administer systemic corticosteroid
therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until
improvement to Grade 1 or less. Upon improvement to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at
least 1 month. Consider administration of other systemic
immunosuppressants in patients whose immune-mediated adverse
reactions are not controlled with corticosteroid therapy.
Immune-Mediated
Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which
may be fatal. The incidence of pneumonitis is higher in patients
who have received prior thoracic radiation.
- IMFINZI as a Single Agent
- In patients who did not receive recent prior radiation, the
incidence of immune-mediated pneumonitis was 2.4% (34/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of
pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3%
(87/475) in patients receiving IMFINZI and 12.8% (30/234) in
patients receiving placebo. Of the patients who received IMFINZI
(475), 1.1% were fatal and 2.7% were Grade 3 adverse
reactions.
- The frequency and severity of immune-mediated pneumonitis in
patients who did not receive definitive chemoradiation prior to
IMFINZI were similar in patients who received IMFINZI as a single
agent or with ES-SCLC or BTC when in combination with
chemotherapy.
- Immune‑mediated pneumonitis occurred in 1.3% (5/388) of
patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and
Grade 3 (0.2%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated pneumonitis occurred in 3.5% (21/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including fatal (0.5%), and Grade 3
(1%) adverse reactions.
Immune-Mediated Colitis
IMFINZI and IMJUDO can cause immune-mediated colitis that is
frequently associated with diarrhea. Cytomegalovirus (CMV)
infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis. In cases of
corticosteroid-refractory colitis, consider repeating infectious
workup to exclude alternative etiologies.
- IMFINZI as a Single Agent
- Immune-mediated colitis occurred in 2% (37/1889) of patients
receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%)
adverse reactions.
- Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%)
adverse reactions. Intestinal perforation has been observed in
other studies of IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated colitis occurred in 6.5% (39/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse
reactions. Intestinal perforation and large intestine perforation
were reported in 0.1% of patients.
Immune-Mediated
Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which
may be fatal.
- IMFINZI as a Single Agent
- Immune-mediated hepatitis occurred in 2.8% (52/1889) of
patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%)
and Grade 3 (1.4%) adverse reactions.
- Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients
receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4
(0.3%) and Grade 3 (4.1%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hepatitis occurred in 3.9% (23/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3
(2%) adverse reactions.
Immune-Mediated
Endocrinopathies
- Adrenal Insufficiency: IMFINZI and IMJUDO can cause
primary or secondary adrenal insufficiency. For Grade 2 or higher
adrenal insufficiency, initiate symptomatic treatment, including
hormone replacement as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889)
of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated adrenal insufficiency occurred in 1.5% (6/388)
of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated adrenal insufficiency occurred in 2.2% (13/596)
of patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.8%) adverse
reactions.
- Hypophysitis: IMFINZI and IMJUDO can cause
immune-mediated hypophysitis. Hypophysitis can present with acute
symptoms associated with mass effect such as headache, photophobia,
or visual field cuts. Hypophysitis can cause hypopituitarism.
Initiate symptomatic treatment including hormone replacement as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 hypophysitis/hypopituitarism occurred in <0.1%
(1/1889) of patients who received IMFINZI.
- IMFINZI with IMJUDO
- Immune-mediated hypophysitis/hypopituitarism occurred in 1%
(4/388) of patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hypophysitis occurred in 1.3% (8/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- Thyroid Disorders (Thyroiditis, Hyperthyroidism, and
Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate
hormone replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated thyroiditis occurred in 0.5% (9/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of
patients receiving IMFINZI.
- Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated thyroiditis occurred in 1.5% (6/388) of
patients receiving IMFINZI and IMJUDO.
- Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- Immune-mediated hypothyroidism occurred in 11% (42/388) of
patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated thyroiditis occurred in 1.2% (7/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy.
- Immune-mediated hyperthyroidism occurred in 5% (30/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.2%) adverse
reactions.
- Immune-mediated hypothyroidism occurred in 8.6% (51/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 immune-mediated Type 1 diabetes mellitus occurred in
<0.1% (1/1889) of patients receiving IMFINZI.
- IMFINZI with IMJUDO
- Two patients (0.5%, 2/388) had events of hyperglycemia
requiring insulin therapy that had not resolved at last
follow-up.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated Type 1 diabetes mellitus occurred in 0.5%
(3/596) of patients receiving IMFINZI in combination with IMJUDO
and platinum-based chemotherapy including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated Nephritis with Renal
Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
- IMFINZI as a Single Agent
- Immune-mediated nephritis occurred in 0.5% (10/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- Immune-mediated nephritis occurred in 1% (4/388) of patients
receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated nephritis occurred in 0.7% (4/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology
Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis.
Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS),
drug rash with eosinophilia and systemic symptoms (DRESS), and
toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1 and
CTLA-4 blocking antibodies. Topical emollients and/or topical
corticosteroids may be adequate to treat mild to moderate
non-exfoliative rashes.
- IMFINZI as a Single Agent
- Immune-mediated rash or dermatitis occurred in 1.8% (34/1889)
of patients receiving IMFINZI, including Grade 3 (0.4%) adverse
reactions.
- Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of
patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and
Grade 3 (1.5%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of
patients receiving IMFINZI in combination with IMJUDO in
combination with platinum-based chemotherapy, including Grade 3
(0.3%) adverse reactions.
Immune-Mediated
Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated
pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388)
of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%)
and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse
Reactions
The following clinically significant, immune-mediated adverse
reactions occurred at an incidence of less than 1% each in patients
who received IMFINZI and IMJUDO or were reported with the use of
other immune-checkpoint inhibitors.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism.
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening
infusion-related reactions. Monitor for signs and symptoms of
infusion-related reactions. Interrupt, slow the rate of, or
permanently discontinue IMFINZI and IMJUDO based on the severity.
See USPI Dosing and Administration for specific details. For Grade
1 or 2 infusion-related reactions, consider using pre-medications
with subsequent doses.
- IMFINZI as a Single Agent
- Infusion-related reactions occurred in 2.2% (42/1889) of
patients receiving IMFINZI, including Grade 3 (0.3%) adverse
reactions.
- Infusion-related reactions occurred in 10 (2.6%) patients
receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Infusion-related reactions occurred in 2.9% (17/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies,
IMFINZI and IMJUDO can cause fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. In females of reproductive potential, verify pregnancy
status prior to initiating IMFINZI and IMJUDO and advise them to
use effective contraception during treatment with IMFINZI and
IMJUDO and for 3 months after the last dose of IMFINZI and
IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and
IMJUDO in human milk; however, because of the potential for serious
adverse reactions in breastfed infants from IMFINZI and IMJUDO,
advise women not to breastfeed during treatment and for 3 months
after the last dose.
Adverse Reactions
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), the most common adverse reactions (≥20%) were
cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis
(34%), upper respiratory tract infections (26%), dyspnea (25%), and
rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%)
were pneumonia (7%) and pneumonitis/radiation pneumonitis
(3.4%)
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), discontinuation due to adverse reactions occurred
in 15% of patients in the IMFINZI arm. Serious adverse reactions
occurred in 29% of patients receiving IMFINZI. The most frequent
serious adverse reactions (≥2%) were pneumonitis or radiation
pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation
pneumonitis and fatal pneumonia occurred in <2% of patients and
were similar across arms
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
and IMJUDO plus platinum-based chemotherapy (n=330), the most
common adverse reactions (occurring in ≥20% of patients) were
nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased
appetite (28%), rash (27%), and diarrhea (22%).
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
in combination with IMJUDO and platinum-based chemotherapy (n=330),
permanent discontinuation of IMFINZI or IMJUDO due to an adverse
reaction occurred in 17% of patients. Serious adverse reactions
occurred in 44% of patients, with the most frequent serious adverse
reactions reported in at least 2% of patients being pneumonia
(11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%),
pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse
reactions occurred in a total of 4.2% of patients.
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), the most common
adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%),
and alopecia (31%). The most common Grade 3 or 4 adverse reaction
(≥3%) was fatigue/asthenia (3.4%)
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), IMFINZI was
discontinued due to adverse reactions in 7% of the patients
receiving IMFINZI plus chemotherapy. Serious adverse reactions
occurred in 31% of patients receiving IMFINZI plus chemotherapy.
The most frequent serious adverse reactions reported in at least 1%
of patients were febrile neutropenia (4.5%), pneumonia (2.3%),
anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD
(1.1%). Fatal adverse reactions occurred in 4.9% of patients
receiving IMFINZI plus chemotherapy
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse
reactions (occurring in ≥20% of patients) were fatigue, nausea,
constipation, decreased appetite, abdominal pain, rash, and
pyrexia
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to
adverse reactions occurred in 6% of the patients receiving IMFINZI
plus chemotherapy. Serious adverse reactions occurred in 47% of
patients receiving IMFINZI plus chemotherapy. The most frequent
serious adverse reactions reported in at least 2% of patients were
cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and
acute kidney injury (2.4%). Fatal adverse reactions occurred in
3.6% of patients receiving IMFINZI plus chemotherapy. These include
ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients),
and upper gastrointestinal hemorrhage (2 patients)
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO, the most common adverse reactions
(occurring in ≥20% of patients) were rash, diarrhea, fatigue,
pruritus, musculoskeletal pain, and abdominal pain
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO, serious adverse reactions occurred in
41% of patients. Serious adverse reactions in >1% of patients
included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia
(2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%),
and anemia (1.3%). Fatal adverse reactions occurred in 8% of
patients who received IMJUDO in combination with durvalumab,
including death (1%), hemorrhage intracranial (0.5%), cardiac
arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and
immune-mediated hepatitis (0.5%). Permanent discontinuation of
treatment regimen due to an adverse reaction occurred in 14% of
patients
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI is indicated for the treatment of adult patients with
unresectable Stage III non-small cell lung cancer (NSCLC) whose
disease has not progressed following concurrent platinum-based
chemotherapy and radiation therapy.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing epidermal growth factor
receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)
genomic tumor aberrations.
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the
treatment of adult patients with unresectable hepatocellular
carcinoma (uHCC).
Please see Full Prescribing Information for
IMFINZI and IMJUDO, including Medication
Guide.
SELECT SAFETY INFORMATION FOR CALQUENCE®
(acalabrutinib)
INDICATION AND USAGE
CALQUENCE is indicated for the treatment of adult patients with
chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
(SLL).
SELECT SAFETY INFORMATION
Serious adverse events, including fatal events, have occurred
with CALQUENCE, including serious and opportunistic infections,
hemorrhage, cytopenias, second primary malignancies, and atrial
fibrillation and flutter. The most common adverse reactions (≥ 30%)
of any grade in patients with CLL were anemia, neutropenia,
thrombocytopenia, headache, upper respiratory tract infection, and
diarrhea.
Please see full Prescribing Information,
including Patient Information.
Notes
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